Screening For Lung Cancer - What You Need to Know

What is the evidence and current recommendations for lung cancer screening?

Screening & Early Detection of Lung Cancer - What You Need to Know

by Dr. C.H. Weaver M.D. updated 11/2018

Lung cancer is the leading cause of cancer death among both men and women in the United States. The disease is often detected at an advanced, difficult-to-treat stage.

One strategy for reducing the death rate from lung cancer is to increase the rate of early detection so that cancers are found when they are most treatable. Currently, only 25 percent of patients are diagnosed with early-stage disease. The US Preventive Services Task Force (USPSTF) has made a significant step toward this goal by recommending screening with annual low-dose computed tomography (CT) scans for people who are at high risk of lung cancer.(1)

Cancer screening involves the use of tests to detect cancer at an early stage in people who don’t have any symptoms of the disease. For cancers such as breast cancer, colorectal cancer, and cervical cancer, screening has contributed to decreased rates of cancer death by detecting these cancers earlier when they are most treatable.

Early detection of lung cancer has proven more difficult. In order for new screening methods to be adopted into routine clinical care, the measures must identify cancer early enough to improve outcomes, must be economically feasible, and must detect cancer with an acceptable degree of accuracy.

Low-dose CT scans are a type of imaging that can identify smaller nodules than chest X-rays, making them a strong candidate for lung cancer screening. Low-dose CT is best used on high-risk individuals (smokers and older individuals, for example because CT scans can have false-positive results, which can lead to unnecessary invasive procedures. In high-risk populations, however, the benefits of screening with low-dose CT scans outweigh the harm.

The USPSTF has made the following reccomendations:

  • Screen people ages 55 to 80 who have....
  • A 30-pack-year or greater history of smoking...
A “pack-year” refers to someone who has smoked an average of one pack of cigarettes per day for a year. Someone who smokes a pack a day will take 30 years to reach 30 pack-years; however, someone who smokes two packs a day will take only 15 years to reach that limit.
  • Who are either current smokers, or who have quit in the past 15 years.
  • The screening should be provided in academic medical centers and other sites with specialized radiologists and surgeons on staff.

Under the new guidelines, about 8 million people would be eligible for annual screening. If all of these people complied with screening guidelines, about 4,000 cancer deaths per year could be prevented.

The researchers concluded that screening lower-risk individuals would offer more harm than benefit.

An Added Benefit Of Stepping Up Lung Cancer Screening

In addition to catching lung cancer in its early and most treatable stages, lung cancer screening may have another major impact: it may help encourage people to quit smoking. Research has found that when screening detects changes that look suspicious for lung cancer, a person is more likely to quit smoking.

How is screening for lung cancer performed?

Currently a computed tomography or "CT" scan is the preferred method for lung cancer screening in high risk individuals. The CT scan is a sensitive imaging test that is conducted with a large machine that is positioned outside the body and rotates to capture detailed images of the organs and tissues inside the body. It’s better than a regular x-ray at finding lung tumors and showing them clearly. That’s why CT scans are used for lung cancer screening.

In addition to cancer however, CT scans also detect other abnormalities that need to be further evaluated. This may lead to additional scans and more-invasive tests such as a needle biopsy or even surgery that can sometimes lead to complications. There is also a risk that comes with increased exposure to radiation from the CT scan, even though a low dose is used for lung screening. For these reasons its important to screen individuals more likely to be at risk for developing lung cancer and avoid the complications of screening in those at minimal risk.

The National Lung Screening Trial (NLST) evaluated chest x ray and CT scan screening in individuals at risk of getting lung cancer. The study included more than 50,000 people considered to be at high risk; age 55 to 74 who were current or former smokers with at least a 30 pack-year history of smoking and who had not quit more than 15 years ago.

The NLST found that low-dose CT identified cancers earlier and that CT screened individuals had a 20% lower chance of dying from lung cancer than those who were screened using chest x-rays.

Private Insurers and Medicare Pay for Lung Cancer Screening

The Centers for Medicare and Medicaid Services (CMS) decided low-dose CT will be reimbursed once a year for Medicare patients who are eligible for lung cancer screening. Patients must be ages 55 to 77, have at least a 30 pack-year history of smoking, and currently smoke or have quit within the past 15 years.

Because lung screening is recommended by the US Preventive Services Task Force (USPSTF), private insurers have also begun covering the tests. However, the criteria for screening eligibility are slightly different. The USPSTF guidelines call for screening up to age 80, Whereas the American Cancer Society (ACS), the American College of Chest Physicians (ACCP), the American Society of Clinical Oncology (ASCO), and the National Comprehensive Cancer Network (NCCN) have an upper age cut off of 74.

What Are The Early Signs and Symptoms of Lung Cancer?

The most common symptoms of lung cancer are:

  • A cough that does not go away or gets worse
  • Chest pain that is often worse with deep breathing, coughing, or laughing
  • Hoarseness
  • Weight loss and loss of appetite
  • Coughing up blood or rust-colored sputum (spit or phlegm)
  • Shortness of breath
  • Feeling tired or weak
  • Infections such as bronchitis and pneumonia that don’t go away or keep coming back
  • New onset of wheezing

Other Studies Evaluating Lung Cancer Screening

According to results recently published in The Lancet, annual screening with low-dose computed tomography (CT) and selected positron-emission tomography (PET) scans appear to detect lung cancer early, when it is most curable.

Researchers from Italy conducted a clinical trial evaluating the use of low-dose spiral CT and PET as screening for lung cancer in over 1,000 individuals who were heavy smokers or had a history of heavy smoking. All patients underwent annual CT screening and subsequent PET screening if a tissue mass on CT was larger than 5 millimeters. Individuals who had a lung mass on CT that was 5 millimeters or less, no action was taken unless the mass had grown by the time of the next annual scan.

Two years following initiation of this trial, lung cancer was detected in 22 patients. All but one of these patients had their cancer detected early enough so that it could be completely surgically removed. Of all the patients in this trial, only 6 had unnecessary biopsies. Overall, 77% of cancers detected were stage I (cancer has not spread from site of origin). At the second screening, 100% of cancers detected were stage I, indicating that cancers measuring 5 millimeters or less do not need immediate biopsies, but can safely be monitored for one year.

The researchers concluded that annual CT followed by PET scans in patients with a lung mass measuring greater than 5 millimeters appears to detect lung cancer in very early stages, allowing for a high degree of complete surgical removal. In addition, unnecessary biopsies were kept to a minimum through this screening regimen.

Annual Computed Tomography Screening Detects Early Lung Cancer

The Early Lung Cancer Action Project was designed to evaluate whether annual CT screening is useful for detecting lung cancer. The baseline results of that study have been previously reported; however, the current study focuses on the early results of the repeat screenings. The study involved a cohort of 1,000 high-risk individuals who were recruited for baseline and annual repeat CT screening. At latest follow-up, a total of 1,184 annual repeat screenings had been performed.

The results of the annual screenings included positive test results in 30 cases; however, in two of these cases, the individuals died of unrelated causes prior to diagnostic workup and the nodules resolved in another 12 of the cases. In the remaining 16 cases, repeat CT scans revealed that eight had further growth and eight had an absence of further growth. Of the eight cases with further growth, five were diagnosed with stage IA non-small cell lung cancer, one was diagnosed with stage IIIA non-small cell lung cancer and one was diagnosed with small cell carcinoma of limited stage. In addition, two more subjects experienced symptoms and were diagnosed with stage IIB non-small cell carcinoma and small cell carcinoma of limited stage.

The researchers concluded that CT screening allows for diagnosis at substantially earlier and more curable stages when compared with no screening. Furthermore, false-positive test results are uncommon. More research is needed to further define the role of CT screening for lung cancer and to determine how frequently high-risk individuals, such as smokers, should be screened. Individuals who smoke or have smoked in the past may wish to speak with their physician about a smoking cessation program and/or possible screening for early lung cancer.

Gene Properties in Sputum May Signal Increased Risk for Developing Lung Cancer

According to an article published in Clinical Cancer Research, methylation, the chemical modification of a gene or multiple genes, identified in sputum may help identify individuals who are at a higher risk of developing lung cancer. Individuals at a higher risk may benefit from more intensive screening schedules.

A multi-institution clinical trial was conducted to evaluate methylation of certain genes in the sputum (saliva) and blood and possible associations with the risk of developing lung cancer. This study included 56 individuals who had been diagnosed with lung cancer, 121 individuals who were smokers but did not have lung cancer, and 74 individuals who were non-smokers. Methylation of specific genes (including O6-methylguanine-DNA methyltransferase, ras effector homologue 1, death associated protein kinase, PAX5alpha, and p16) had significant associations with risks of developing lung cancer:

  • Patients with lung cancer had over a 6-fold increased rate of methylation of three or more genes in the sputum than smokers with no cancer.
  • Patients with lung cancer had over a 3-fold increased rate of methylation of just one or more genes than non-smokers.

The researchers concluded that methylation of specific genes may indicate an increased risk of developing lung cancer. Patients with this high risk may benefit from more intense screening than their counterparts; this should increase the rate at which lung cancer is detected at its earliest and most treatable stages.

According to an article recently published in the American Journal of Respiratory and Critical Care Medicine, individuals with family members who have been diagnosed with lung cancer are at an increased risk of developing lung cancer themselves.

Although there is a strong association between smoking and the development of lung cancer, it is becoming clear that there may be a genetic link to the disease as well, placing family members of an individual diagnosed with lung cancer at a higher risk of developing the disease than the general population – regardless of smoking status. Ultimately, these findings may allow for the placement of these high risk individuals into appropriate screening clinical trials and subsequent standard screening programs for lung cancer.

Researchers from Michigan conducted a study to further evaluate a possible genetic link to lung cancer. They reviewed literature from studies containing family history of individuals who had been diagnosed with lung cancer, chronic obstructive pulmonary disease (COPD), laryngeal and pharyngeal cancer.

• Nearly 14% of individuals in a study including over 26,000 lung cancer patients had at least one first-degree relative who had also been diagnosed with lung cancer.
• The mean age for an individual to develop lung cancer was 60 years in those with a family history of the disease, compared with 70 years in those who did not have a family history.
• Alterations on specific regions on chromosomes 6 and 12 were linked to an increased risk of lung cancer.

The researchers concluded that this study warrants further evaluation of a genetic link to lung cancer. They also stated that individuals with a strong family history who are smokers or current smokers should speak with their physician regarding referral into a screening program, or into a clinical trial that evaluates different screening methods to detect lung cancer early.

Screening with Chest X-Rays Does Not Reduce Lung Cancer Mortality

Results from the PLCO (Prostate, Lung, Colorectal, and Ovarian) Cancer Screening Trial provide convincing evidence that using chest x-rays to screen for lung cancer does not reduce lung cancer deaths. These results were published in the Journal of the American Medical Association.

The PLCO Cancer Screening Trial compared chest x-rays (every year for four years) to usual care (no screening) among almost 155,000 people between the ages of 55 and 74.[2]

  • During the 13 years of the study, there were 1,213 lung cancer deaths in the chest x-ray group and 1,230 in the usual care group. The small difference between the two groups was not statistically significant (could have occurred by chance alone).

These results indicate that annual screening with chest x-ray does not reduce lung cancer mortality.

References:

  1. U.S. Preventive Services Task Force Recommends Lung Cancer Screening for High-Risk Populations in Final Statement [news bulletin]. USPSTF website. Available at: http://www. uspreventiveservicestaskforce.org/Page/Name/ newsroom#2013. Accessed October 16, 2015.
  2. Tammemägi MC, Berg CD, Riley TL, Cunningham CR, Taylor KL. Impact of lung cancer screening results on smoking cessation. Journal of the National Cancer Institute. 2014;106(6):dju084. doi: 10.1093/jnci/dju084.
  3. https://www.uspreventiveservicestaskforce.org/Page/Document/UpdateSummaryFinal/lung-cancer-screening
  4. The National Lung Screening Trial Research Team. Reduced lung-cancer mortality with low-dose computed tomographic screening. New EnglandJournal of Medicine. 2011;365:395-409.
  5. Oken MM, Hocking WG, Kvale PA et al. Screening by chest radiograph and lung cancer mortality. The Prostate, Lung, Colorectal, and Ovarian (PLCO) Randomized Trial. Journal of the American Medical Association. Early online publication October 26, 2011.
  6. American Cancer Society. Can non-small cell lung cancer be found early? Last revised September 15, 2011.
  7. Ma J, Ward EM, Smith R, et al. Annual number of lung cancer deaths potentially avertable by screening in the United States. Cancer. 2013; 119(7): 1381-1385.
  8. Bach PB, Mirkin JN, Oliver TK, et al. Benefits and harms of CT screening for lung cancer: A systematic review. Journal of the American Medical Association. Published early online May 20, 2012: doi:10.1001/jama.2012.5521
  9. Belinsky S, Klinge D, Dekker J, et al. Gene Promoter Methylation in Plasma and Sputum Increases with Lung Cancer Risk. Clinical Cancer Research. 2005; 11, 6505-6511.
  10. Pastorino U, Bellomi M, Landoni C, et al. Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results. The Lancet. 2003;362:593-597.
  11. Strauss GM, Dominioni L, Jett JR, et al. Como International Conference Position Stagement. Lung Cancer Screening for Early Diagnosis 5 Years After The 1998 Varese Conference. Chest 2005;127:1146-1151.
  12. Pastorino U, Bellomi M, Landoni C, et al. Early lung-cancer detection with spiral CT and positron emission tomography in heavy smokers: 2-year results. The Lancet. 2003;362:593-597.

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